HMP shunt/Pentose Phosphate and Fermentation Pathway

2. • In most animal tissues, the major catabolic fate of glucose 6-phosphate is glycolytic breakdown to pyruvate, much of
which is then oxidized via the citric acid cycle, ultimately leading to the formation of ATP.
• In biochemistry, the pentose phosphate pathway (also called the phosphogluconate pathway and the hexose
monophosphate shunt) is a metabolic pathway parallel to glycolysis that generates NADPH and pentoses (5- carbon
sugars) as well as Ribose 5-phosphate, a precursor for the synthesis of nucleotides.
• In this oxidative pathway, NADP+ is the electron acceptor, yielding NADPH. Rapidly dividing cells, such as those of
bone marrow, skin, and intestinal mucosa, and those of tumors, use the pentose ribose 5-phosphate to make RNA, DNA,
and such coenzymes as ATP, NADH, FADH2, and coenzyme A.
• Tissues that carry out extensive fatty acid synthesis(liver, adipose, lactating mammary gland) or very active synthesis of
cholesterol and steroid hormones (liver, adrenal glands, gonads) require the NADPH provided by this pathway.
Erythrocytes and the cells of the lens and cornea are directly exposed to oxygen and thus to the damaging free radicals
generated by oxygen.
• By maintaining a reducing atmosphere (a high ratio of NADPH to NADP+ and a high ratio of reduced to oxidized
glutathione), such cells can prevent or undo oxidative damage to proteins, lipids, and other sensitive molecules.

4. There are two phases in the HMP Shunt:- Oxidative phase and Non-Oxidative phase
Oxidative Phase: The first reaction of the pentose phosphate pathway is the oxidation of glucose 6
phosphate by glucose 6-phosphate dehydrogenase (G6PD) to form 6-phosphoglucono-d-lactone, an
intramolecular ester. NADP+ is the electron acceptor, and the overall equilibrium lies far in the direction of
NADPH formation. The lactone is hydrolyzed to the free acid 6-phosphogluconate by a specific lactonase,
then 6-phosphogluconate undergoes oxidation and decarboxylation by 6-phosphogluconate
dehydrogenase to form the ketopentose ribulose 5-phosphate; the reaction generates a second molecule of
NADPH. (This ribulose 5-phosphate is important in the regulation of glycolysis and gluconeogenesis
Phosphopentose isomerase converts ribulose 5-phosphate to its aldose isomer, ribose 5-phosphate. In
some tissues, the pentose phosphate pathway ends at this point, and its overall equation is:
Glucose 6-Phosphate + 2 NADP+ + H2O Ribose 5-Phosphate + 2 NADPH + CO2 + 2H+
The net result is the production of NADPH, a reductant for biosynthetic reactions, and ribose 5-phosphate,
a precursor for nucleotide synthesis

5. The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate:
• In tissues that require primarily NADPH, the pentose phosphates produced in the oxidative phase of the
pathway are recycled into glucose 6-phosphate.
• In this nonoxidative phase, ribulose 5-phosphate is first epimerized to xylulose 5-phosphate Then, in a
series of rearrangements of the carbon skeletons six five-carbon sugar phosphates are converted to five
six-carbon sugar phosphates, completing the cycle and allowing continued oxidation of glucose 6
phosphate with production of NADPH.
• Continued recycling leads ultimately to the conversion of glucose 6-phosphate to six CO2. Two
enzymes unique to the pentose phosphate pathway act in these interconversions of sugars: transketolase
and transaldolase. Transketolase catalyzes the transfer of a two carbon fragment from a ketose donor
to an aldose acceptor.
• In its first appearance in the pentose phosphate pathway, transketolase transfers C-1 and C-2 of
xylulose 5-phosphate to ribose 5-phosphate, forming the seven-carbon product sedoheptulose 7-
phosphate.

6. • The remaining three carbon fragment from xylulose is glyceraldehyde 3-
phosphate. Next, transaldolase catalyzes a reaction of three-carbon fragment is
removed from sedoheptulose 7-phosphate and condensed with glyceraldehyde 3-
phosphate, forming fructose 6-phosphate and the tetrose erythrose 4-phosphate.
• Now transketolase acts again, forming fructose 6-phosphate and glyceraldehyde
3-phosphate from erythrose 4-phosphate and xylulose 5-phosphate. Two
molecules of glyceraldehyde 3-phosphate formed by two iterations of these
reactions can be converted to a molecule of fructose 1,6-bisphosphate as in
gluconeogenesis, and finally FBPase-1 and phosphohexose isomerase convert
fructose 1,6-bisphosphate to glucose 6-phosphate. Overall, six pentose
phosphates have been converted to five hexose phosphates the cycle is now
complete

7. • All the enzymes in the pentose phosphate pathway are located in the cytosol, like those
of glycolysis and most of those of gluconeogenesis. In fact, these three pathways are
connected through several shared intermediates and enzymes.
• The glyceraldehyde 3-phosphate formed by the action of transketolase is readily
converted to dihydroxyacetone phosphate by the glycolytic enzyme triose phosphate
isomerase, and these two trioses can be joined by the aldolase as in gluconeogenesis,
forming fructose 1,6-bisphosphate.
• Alternatively, the triose phosphates can be oxidized to pyruvate by the glycolytic
reactions. The fate of the trioses is determined by the cell's relative needs for pentose
phosphates, NADPH, and ATP.

8. • In respiring organisms, both aerobic and anaerobic, most of the energy is produced
by electron transport phosphorylation. This is in contrast to fermentations, in which
most of the adenosine triphosphate (ATP) is synthesized by substrate level
phosphorylation.
• Fermentation is an anaerobic redox process, in which the oxidation of the substrate
is coupled to the reduction of another substrate or an intermediate derived from the
oxidation, with the difference in redox potential of the substrate and the end
product providing energy for ATP synthesis.
• In fermentation, the substrate is only partly oxidized, and, therefore, only a small
amount of the energy stored in the substrate is conserved

9. • Glycolysis is the first stage of fermentation.
• Forms 2 pyruvate, 2 NADH, and 2 ATP
• Pyruvate is converted to other molecules, but is not fully broken
down to CO2 and water.
• Regenerates NAD+ but doesn’t produce ATP
• Provides enough energy for some single-celled anaerobic
species.
• Fermentations are carried out by a wide range of organisms,
many of which occupy anaerobic niches, and they yield a
variety of end products, some of which find commercial uses.

10. a) Alcoholic Fermentation and b) Lactic Acid Fermentation

11. Ethanol is the reduced product of Alcoholic or Ethanol Fermentation.
Yeast and other microorganisms ferment glucose to ethanol and CO2, rather than to lactate. Glucose is
converted to pyruvate by glycolysis, and the pyruvate is converted to ethanol and CO2 in a two-step process:
In the first step, pyruvate is decarboxylated in an irreversible reaction catalyzed by pyruvate decarboxylase.
This reaction is a simple decarboxylation and does not involve the net oxidation of pyruvate. Pyruvate
decarboxylase requires Mg2+ and has a tightly bound coenzyme, thiamine pyrophosphate. In the second step,
acetaldehyde is reduced to ethanol through the action of alcohol dehydrogenase, with the reducing power
furnished by NADH derived from the dehydrogenation of glyceraldehyde 3-phosphate. This reaction is a
well-studied case of hydride transfer from NADH. Ethanol and CO2 are thus the end products of ethanol
fermentation, and the overall equation is:
Glucose + 2ADP + 2Pi 2 ethanol + 2CO2 + 2ATP + 2H2O

12. Lactic Acid Fermentation:
Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation. When animal tissues cannot be supplied
with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis, NAD1 is
regenerated from NADH by the reduction of pyruvate to lactate. Some tissues and cell types (such as
erythrocytes, which have no mitochondria and thus cannot oxidize pyruvate to CO2) produce lactate from glucose
even under aerobic conditions. The reduction of pyruvate in this pathway is catalyzed by lactate dehydrogenase,
which forms the L isomer of lactate at pH 7:

13. • The overall equilibrium of the reaction strongly favours lactate formation. In glycolysis,
dehydrogenation of the two molecules of glyceraldehyde 3-phosphate derived from each
molecule of glucose converts two molecules of NAD+ to two of NADH. Because the
reduction of two molecules of pyruvate to two of lactate regenerates two molecules of
NAD+, there is no net change in NAD+ or NADH.
• The lactate formed by active skeletal muscles (or by erythrocytes) can be recycled; it is
carried in the blood to the liver, where it is converted to glucose during the recovery from
strenuous muscular activity.
• When lactate is produced in large quantities during vigorous muscle contraction (during a
sprint, for example), the acidification that results from ionization of lactic acid in muscle
and blood limits the period of vigorous activity.
• Some of the energy of the glucose molecule has been extracted by its conversion to lactate
enough to give a net yield of two molecules of ATP for every glucose molecule consumed